Cancer cachexia: assessment and classification. KCH Fearon University of Edinburgh Scotland

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1 Cancer cachexia: assessment and classification KCH Fearon University of Edinburgh Scotland 1

2 What is the cancer cachexia phenotype?...the shoulders, clavicles, chest and thighs melt away. This illness is fatal... Hippocrates BC CACHEXIA V STARVATION? 2

3 Change in Nutritional Status in Malnourished Cancer and Non-Cancer Patients during EN + Δ Weight (kg) Δ alb (g/l) Δ TSF Δ MMA (% of (% of standard) standard) Cancer (n=6) 3.5(2-7) 0.0( ) 0.3) 14.5(3-29) 3(3-13) Non-cancer 9(7-13)* 3.0(0.3-11) 11(7-18) 18) 10.5(9-13)** 13)** (n=5) *p<0.01, **p<0.05, *EN: Kcal/d, g 0.2g N/Kg/d Nixon et al,1981; Cancer Res.: Cachexia A clinical syndrome characterised by anorexia early satiety weight loss muscle wasting anaemia oedema Calman KC

4 Definition of cancer cachexia Cachexia = Weight loss > 10% CRP > 10 mg/l Food intake < 1500 kcal Definition of cachexia Evans WJ et al. Cachexia: a new definition. Clin Nutr,

5 Definition and classification of cancer cachexia: an international consensus framework Fearon KCH, Strasser F, Anker SD, Bosaeus I, Bruera E, Fainsinger R L, Jatoi A, Loprinzi C, MacDonald N, Mantovani G, Davis M, Muscaritoli M, Ottery F, Radbruch L, Ravasco P, Walsh D, Wilcock A, Kaasa S, Baracos V Lancet Oncology 2011, e-pub What does a classification system need to do? Diagnostic Staging Assessment Management Criteria Domains Need to Address: obesity aged Needs to Identify: Early phase (prophylaxis) Late phase (symptomatic only) Mechanisms need to be: Evaluated/ranked according to: importance reversibility impact needs to be measured: routine clinical practice research clinical trials Education/ policy mass/function pyschosocial distress 5

6 Definition Cancer cachexia is a multifactorial syndrome defined by an ongoing loss of skeletal muscle mass (with or without loss of fat mass) that cannot be fully reversed by conventional nutritional support and leads to progressive functional impairment. The pathophysiology is characterised by a negative protein and energy balance driven by a variable combination of reduced food intake and abnormal metabolism. Diagnosis Involuntary weight loss >5% over last 6 months (in absence of simple starvation) OR Weight loss >2% with BMI <20 OR Weight loss >2% with an appendicular skeletal muscle index consistent with sarcopenia (males <7.26 kg/m 2 ; females <5.45 kg/m 2 )* * With fluid retention, a large tumour mass or overweight/obesity a direct measure of muscularity is particularly recommended. 6

7 Definition of cachexia CACHEXIA DIAGNOSIS CANCER BOTH weight loss > 5% in 6 months absence of starvation Fearon K et al. Lancet Oncology 2011 Severity Relative to risk of loss of QoL or survival duration 7

8 Risk is not uniform! Physiological risk from losing weight is related to initial body mass % Change

9 $6M Question Will staff at a busy oncology clinic calculate %weightloss and BMI? Phases of cancer cachexia - Pre-cachexia Cachexia Refractory cachexia Normal Death Weight loss 5% Metabolic/endocrine change Weight loss > 5% Often r Often reduced food Intake/Systemic Inflammation Low performance score Immunocompromised <3 months expected survival 9

10 Original Model Pre-cachexia Cachexia Refractory Cachexia New Model Weight-stable Non-cachexia Pre-cachexia Cachexia Pre-refractory Cachexia Refractory Cachexia Assessment 10

11 Four Domains of the Conceptual Framework I. Depletion of Reserves II. Limitation of food intake III. Catabolic Drivers IV. Impact and outcomes Assessment Domains Anorexia/reduced food intake Catabolic drivers Muscle mass and strength Impact drive to eat anorexia chemosensory disturbance upper GI motility distal GI dysmotility food intake esp protein (g/d) systemic inflammation tumour progression insulin resistance hypogonadism use of steroids muscle mass -CT/MRI -DEXA -Anthropometry -BIA muscle strength -dynamometry physical functioning -patient reported (EORTC QLQ -C30) -physician reported (WHO/Karnofsky) -activity meter psychosocial distress secondary causes of impaired intake 11

12 Past Present Future STORES Stable Weight kg Weight kg Weight Loss % Duration WL BMI Active Weight Loss m kglm2 Y / N For Prevention (Pre-cachexia) Y / N Therapy For Repletion (BMI <20, Weight Loss > 10%) Y / N Therapy INTAKE Loss of Appetite Early Satiety Loss of Intake Y / N Y / N Kcal/d Requires Intake Target intake Kcal/d PERFORMANCE Secondary anorexia: Pain Y / N Depression Y / N Constipation Y / N Obstruction Y / N Performance Score (0-4) Treat primary anorexia Treat secondary anorexia Activity: ADL s Y / N Exercise Y / N POTENTIAL Cancer Type Cancer Stage (I-IV) Goals of Therapy: Cure Y / N Control Y / N Palliation Y / N Expectations: appetite Intake Weight Activity Y / N Y / N Y / N Y / N Bloods: C-reactive Protein mg/l Albumin g/l Haemoglobin g/l Therapy: Chemotherapy Y / N Radiotherapy Y / N Opiates Y / N Likely Course of Cancer (3m): Progress Y / N Stable Y / N Regress Y / N Survival expectation: <3m Y / N 3-6m Y / N >6m Y / N Patient-Generated Subjective Global Assessment (PGSGA) Reserves % weight loss 1 and 6 months Physical exam of 7 fat depots and muscle groups Food intake Subjective scale: normal very little of anything 13 nutrition impact symptoms Yes/No Catabolic Drivers Cancer Stage Corticosteroid Tx Fever Old age, comorbidities Impact Performance status 0-4 Mini-Nutritional Assessment (MNA) Reserves % weight loss 3 months Body mass index, calf and mid-arm circumference Food intake Subjective decline 0,1,2 # of meals / day Protein rich foods Fluid intake Fruit / Veg intake Assistance required to eat Catabolic Drivers Psychological distress or acute disease Dementia or depression Sores or ulcers >3 prescription drugs Impact Mobility 0-2 Self-view of health and nutritional status Lives independently 12

13 The Missing Link Definition Classification Assessment Therapeutic Evidence Base 13

14 RCTs 14

15 Summary New classification framework for cancer cachexia is evolving but needs further validation The EBM treatment of cachexia should inform assessment RCTs are required.enrol in MENAC! Strategies for intervention in cachexia Anorexia + Metabolic change = Cachexia Increased food intake + Modulation of metabolism = Reversal of cachexia 15

Four Domains of the Conceptual Framework I.

Catabolic Drivers IV. Impact and outcomes e.g.

Sarcopenia (severe muscle wasting) Nutrition impact

Inflammation Tumor burden Insulin resistance Hypogonadism

16 Four Domains of the Conceptual Framework I. Depletion of Reserves II. Limitation of food intake III. Catabolic Drivers IV. Impact and outcomes e.g. e.g. e.g. e.g. Underweight Weight loss Lean tissue wasting Sarcopenia (severe muscle wasting) Nutrition impact symptoms: Anorexia Dysphagia Nausea Social / psychological Inflammation Tumor burden Insulin resistance Hypogonadism Corticosteroids Comorbidities Physical function Quality of life Distress Survival Treatment outcomes Costs 16

Classification of (cancer) cachexia: Any improvements to expect?

6 th Research Congress of EAPC Glasgow, June 11th 2010 Session Cachexia of EPCRC and EAPC RN Classification of (cancer) cachexia: Any improvements to expect? The joint work of many persons involved, thank